Despite minor geographic shifts, the Stroke Belt, a region of highest stroke mortality in the Southeastern US identified a half century ago, still persists today. Recent studies have found that the stroke mortality is also higher among children in the Southeast, thus environmental factors have been hypothesized contributing to the Stroke Belt in addition to other hypotheses on lifestyle and social-economic status. For decades, it has been demonstrated outside the US that geographic variations in trace elements may play critical roles in the development of cardiovascular diseases. However, the geographic variation of trace element levels in relation to stroke risk remains unclear. The overall objectives of this project ae to examine the associations between trace element levels and stroke risk and to investigate whether geographic variation of trace element levels is related to the Stroke Belt. We propose a case-cohort study, which will include incident ischemic stroke cases (n=~620) and a sub-cohort (n=~2500) of non-stroke cases randomly sampled within region-race-sex stratum from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, an ongoing US national population-based, general population cohort of 30,239 African American and Caucasian adults, aged 45 and older at baseline (2003-2007). The proposed study will focus on arsenic, cadmium, mercury, magnesium and selenium. Specifically, we will characterize the distribution of trace element levels measured in urine or serum according to demographic and geographic characteristics of study participants; and to examine prospective associations between trace element levels and risk of stroke. This research will help identify at-risk individuals for stroke, thus providing important data identifying whether stroke risk can be reduced by dietary, supplemental, lifestyle or environmental interventions that modify trace element patterns.